The objectives of this proposed research are to study the mechanism of carcinogenesis and chemoprevention of colorectal cancer. Human colorectal cancer is a major problem in the United States and is second only to lung cancer as a cause of death. A surgical bypass colostomy model to study colorectal carcinogenesis in rats is proposed. In this model, a short loop of colon at the junction of the transverse and descending colon will be placed surgically out of the abdominal wall to create two openings. The proximal one is the exit for feces and the distal one is for introduction of carcinogens and other modifiers of carcinogenesis. A micro colonoscopic technique will be developed to monitor the progress of tumorigenesis in the colon. In the phase I project the bypass colostomy model will be performed in Sprague-Dawley rats. The effects of the carcinogens, 1,2-dimethylhydrazine, methylazoxymethanol acetate and N-methyl-N-nitrosourea will be tested by applying locally via colostomy and/or systemically. The tumorigenic response of the bypassed colon with respect to the route of carcinogen administration will be evaluated.